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There needs to be more research on Opioid painkillers and Enkephalins!

Chronic pain is something that most people have to go through every day, such as back pain caused by sciatica or other reasons, headaches, migraines or other neurological pains. To help get people through the difficult pain, several painkillers have been produced and a widely used such as codeine and morphine (sometimes codeine is given as co-codamol, a mix of codeine and paracetamol). Even though opioids are great painkillers they are also very
addictive and are abused greatly, resulting in many tragic deaths due to drug overdose.
More research goes into creating a drug that has the same chemical properties
as endogenous opioids but without having a high abuse potential, however
ongoing research is difficult and new possible drugs come out to be addictive
also, therefore defeating the purpose of the drug.

Where opioid research
was originally derived from [1]:

Enkephalins (enkephalins is a Greek word meaning “in the
head”) are naturally found in the body. They are a variety of peptides and
proteins which are analgesics and consist of 5 amino acids (pentapeptides). There
are 2 types of Enkephalins:Met-Enkephalins [H-TYR-GLY-GLY-PHE-MET-OH] and Leu-Enkephalins [H-TYR-GLY-GLY-PHE-LEU-OH].
Both Enkephalins are pentapeptides (consisting of 5 amino acids) and have
preference for the δ(delta)- opioid receptor.

Enkephalins work as the body’s natural painkillers and are derived
from three inactive precursor proteins called proenkephalins. The endogenous
opioids also consist of a peptide chain which is responsible for targeting each
peptide to particular type of opioid receptor (mu µ, kappa, κ,
or delta, δ).

The Enkephalins have a remarkable structure which includes a
fragment that is found in opioid drug derivatives. By looking at structure
activity relationships (SARs) between morphine and met-enkephalin; there is a
tyrosine skeleton in the morphine skeleton which is beneficial for the activity
of the drug at the receptor. If it is replaced all activity is lost.

By using this piece
of valuable information lots of research goes into developing an analgesic that
does not have many side effects and low abuse potential. For example morphine
is the mostly used opioid drug however it has difficult side effects such as
dysphoria and hallucinations.

So much research goes into creating an analgesic, which is a
derivative of the endogenous opioids and with little to no side effects and is
not addictive like morphine. Opiates such as morphine and codeine have several
side effects such as constipation, nausea, vomiting, itching, and overall
negative effects on patients well being even though they are good analgesics.

Pentazocine was synthesized to find a drug that was an
effective analgesic and at the same time has low abuse potential. Pentazocine
also has mixed agonist and antagonist binding properties at the opioid
receptors which has the potential to be addictive and abused. Since this was
discovered, pentazocine was given a lower analgesic activity and is not widely
used.

Another drug has been approved by the FDA called Zohydro (hydrocodone). However there has been so much criticism around it because it is
a prolonged-release drug (meaning it is not metabolised straight away and only
a small concentration of drug is released into the blood stream every hour).

Hydrocodone
can treat chronic pain and is prescribed in 50 milligrams which is higher than
other hydrocodone containing prescribed medicines.Hydrocodone has been approved by the FDA due to the fact
that the “benefits of the product outweigh the risks”[5,6] although critics have been fighting to reverse the
approval because Zohydro pill can be misused easily by drug addicts.

To conclude, pain research is a wide open sea and a lot of
research goes into opioid painkillers although there are still significant
challenges in finding novel pain therapeutics without having the possibility to
be misused and little side effects.